Preclinical models of serous endometrial cancer from diverse patient populations

Project Summary / Abstract: This administrative supplement is in response to the Notice of Special Interest (NOSI): Administrative Supplements for the Study of the Diverse Aspects of Uterine Serous Carcinoma (Clinical Trial Not Allowed) Notice Number: NOT-CA-24-044. This supplement is a natural extension of the research supported by the

University of Iowa Holden Comprehensive Cancer Center CCSG grant (P30 CA86862) and addresses the need for better preclinical models of serous endometrial cancer that represent diverse patient populations. Uterine endometrial cancer is the 4th most common cancer in females and is unique among cancers in that both incidence

and deaths have increased each year from 2008-2017. Indeed, endometrial cancer is projected to overtake ovarian cancer as the most deadly gynecologic malignancy this year and surpass colorectal cancer incidence and deaths in females by 2030. Serous endometrial cancer refers to a specific histologic subtype of endometrial

cancer and is typified by mutations in the tumor suppressor TP53. While cases of serous histology represent the minority of all endometrial cancer cases (~10%), it is very deadly, with a 37% 5-year survival rate. Endometrial cancer is a disease of racial, ethnic and geographic disparity, with a lower 5-year survival for Black vs. White

females regardless of stage at diagnosis. For reasons that we do not understand, Black patients have a much higher rate of diagnosis with serous endometrial cancer and worse outcomes, even when stratified by treatment and socioeconomic factors. To address the disparities in outcomes for endometrial cancer, we urgently need

better preclinical models that reflect the diversity of the endometrial cancer patient population. Of the available serous-like endometrial cancer cell lines, most are generated from Asian or White patients. Our group has amassed a living biobank of over 150 endometrial cancer PDOs that span the various histologic and molecular

subtypes of endometrial cancer. In this supplement, our objective is to build upon our existing capabilities to expand representation of diverse patient populations in the endometrial cancer PDO biobank, with a special emphasis on Black patients. Our goal is to create 20 PDO models. Serous endometrial tumors and paired

peripheral blood samples will be collected from patients from underrepresented minority groups (with a focus on Black patients) undergoing cytoreductive surgery for suspected diagnosis of endometrial cancer. PDOs will be created with patient tumors. We will validate models for similarity to the primary tumor and compare sensitivity

in vitro with clinical response. We will also partner with community groups to host education sessions about de- identified specimen use, efforts to maintain patient privacy and research integrity, and what will be achieved by studying their tumors. This project is anticipated to have a positive impact on serous endometrial cancer by

significantly expanding preclinical models from diverse patient populations. These models and corresponding sequencing and therapeutic response data will be made available to the academic research community.